DESCRIPTION: The ability to induce the regression of a well established tumor burden via "therapeutic vaccination" is currently limited. One explanation for this is that mechanisms that normally prevent inappropriate attack against "self" antigens expressed by normal tissues may blunt the ability to respond to antigens expressed by tumors. A critical question in tumor immunology is whether antigen presented by progressively expanding tumor cell populations results in T cell tolerance, and, if so, if this state is reversible. Utilizing TCR transgenic mice specific for a model tumor antigen expressed on a B cell lymphoma, the investigator has obtained evidence supporting the existence of tumor-induced antigen specific tolerance that develops with tumor progression. The overall objective of this project is to further characterize this state, focusing on the mechanism of its induction, the settings in which it occurs, and an exploration of its reversibility in the context of active immunotherapy.